Method for the treatment of water-living animals with health modifying agents

Abstract

A process is described for the introduction of health and/or welfare modifying agents, such as vaccines, to water-living animals such as fish. The health and/or welfare modifying agents are introduced into and across an epithelial membrane, such as the gill membrane, of the water-living animal by contacting the animal with the vaccine and then subjecting the animal to a negative pressure differential followed by a rapid release of the negative pressure, by contacting the epithelial membrane with a hyperosmotic concentration of a membrane permeability altering agent, either simultaneously with or prior to contacting the animal with the health and/or welfare modifying agent, or by contacting the epithelial membrane with a hyperosmotic concentration of a membrane permeability altering agent either simultaneously with or prior to contacting the animal with the health and/or welfare modifying agent followed by subjecting the animal to a negative pressure differential and then a rapid release of the negative pressure. Subjecting the animal to a negative pressure differential followed by a rapid release of the negative pressure results in a forceful infiltration of the health and/or welfare modifying agent into the body cavities of the animal. The membrane permeability altering agent renders the epithelial membrane reversibly permeable to the health and/or welfare modifying agent. Effective membrane permeability altering agents include chemical compounds having a molecular weight of about 58 to about 61, with the most preferred membrane permeability altering agents being selected from the group consisting of acetamide, urea, sodium chloride and mixtures thereof.

What is claimed is: 
     
       1. A method of enhancing the penetration into and across an epithelial membrane barrier of a water-living animal of a health modifying agent capable of eliciting a desired health modifying effect therefrom comprising contacting the water-living animal with a sufficient amount of an aqueous solution or dispersion of the health modifying agent to produce the desired health modifying effect on the water-living animal and a solution comprising a sufficient concentration of a second agent selected from the group consisting of acetamide, urea, sodium chloride and mixtures thereof to enhance penetration and systemic uptake of the health modifying agent to achieve the desired health modifying effect. 
     
     
       2. The method of claim 1 wherein the solution comprising the second agent comprises a hyperosmotic concentration of the second agent. 
     
     
       3. A method of treating water-living animals to impart a health modifying agent thereto, comprising contacting water-living animals with a solution comprising a hyperosmotic concentration of a second agent selected from the group consisting of acetamide, urea, sodium chloride and mixtures thereof, and contacting the water-living animals with a health modifying agent for a sufficient period of time for the water-living animals to absorb said health modifying agent. 
     
     
       4. The method of claims 2 or 3 wherein the water-living animal is contacted with the health modifying agent in a soluble or colloidally dispersed mixture comprising the health modifying agent and the second agent. 
     
     
       5. The method of claim 4 wherein the mixture is contacted with the water-living animal for a period of about 3 to about 10 minutes or more. 
     
     
       6. The method of claims 2 or 3 wherein the water-living animal is contacted with the second agent prior to contacting the membrane with the health modifying agent. 
     
     
       7. The method of claim 6 wherein the water-living animal is contacted with the second agent for a period of about 3 to about 10 minutes and then contacted with the health modifying agent for a period of about 2 to about 5 minutes. 
     
     
       8. The method of claims 2 or 3 wherein the concentration of the second agent is at least about 3 times its isosmotic concentration. 
     
     
       9. The method of claims 2 or 3 wherein the second agent comprises a 1 mol:1 mol ratio aqueous mixture of acetamide to sodium chloride. 
     
     
       10. The method of claims 2 or 3 wherein the membrane permeability altering agent comprises a 1 mol:2 mol ratio aqueous mixture of urea to sodium chloride. 
     
     
       11. The method of claims 2 or 3 which further comprises purifying the second agent prior to contacting the water-living animal with the second agent by passing the second agent through a bed of activated charcoal. 
     
     
       12. The method of claims 2 or 3 wherein the second agent further comprises an amount of 2-(4-thiazolyl) benzimidazole effective to enhance said method. 
     
     
       13. The method of claims 2 or 3 wherein the water-living animal is contacted with the second agent by immersing the animal in the aqueous solution of the second agent. 
     
     
       14. The method of claims 2 or 3 wherein the water-living animal is contacted with the health modifying agent by immersing the animal in an aqueous solution or dispersion of the health modifying agent. 
     
     
       15. The method of claims 2 or 3 wherein the water-living animal is contacted with the second agent while the animal is either partially or totally out of water. 
     
     
       16. The method of claims 2 or 3 wherein the water-living animal is contacted with the health modifying agent while the animal is either partially or totally out of water. 
     
     
       17. The method of claims 2 or 3 wherein the aqueous solution or dispersion of the health modifying agent has a viscosity less than about 10 cp. 
     
     
       18. The method of claims 2 or 3 wherein the water-living animals are fish. 
     
     
       19. The method of claims 2 or 3 wherein the health modifying agent is an antigen. 
     
     
       20. The method of claims 2 or 3 wherein the health modifying agent is a chemotherapeutant. 
     
     
       21. The method of claim 19 wherein the antigen is infectious hematopoietic necrosis. 
     
     
       22. The method of claim 19 wherein the antigen is Vibrio anguillarum bacterin. 
     
     
       23. The method of claim 19 wherein the antigen is Aeromonas salmonicida bacterin. 
     
     
       24. The method of claim 19 wherein the antigen is Bovine serum albumin vaccine. 
     
     
       25. The method of claim 19 wherein the antigen is Enteric Redmouth bacterin. 
     
     
       26. The method of claim 19 wherein the antigen is Infectious pancreatic necrosis. 
     
     
       27. A method of treating water-living animals comprising immersing said animals in a solution comprising a hyperosmotic concentration of an agent selected from the group consisting of acetamide, urea, sodium chloride and mixtures thereof, and further comprising a health modifying agent in a sufficient amount to be taken up by said animals. 
     
     
       28. A method of improving the health and/or welfare of water living animals comprising treating said animals with a solution comprising a hyperosmotic concentration of an agent selected from the group consisting of acetamide, urea, sodium chloride and mixtures thereof and further comprising a health and/or welfare enhancing agent in a sufficient amount to be taken up by said animals.